Chronic Diseases and Translational Medicine最新文献

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Goiter is defined as the enlargement of the thyroid gland. It is currently divided into diffuse and nodular and subdivided into toxic (associated with hyperthyroidism) or nontoxic (associated with normal thyroid stimulating hormone [TSH] levels).¹ The most common cause of goiter is iodine deficiency,² and other causes are increased levels of TSH, natural goitrogens, iron and vitamin A deficiency, genetic factors (DICER1 syndrome and PTEN hamartoma tumor syndrome), and hereditary (Plummer syndrome) factors.³

A rare entity known as familial Mediterranean fever (FMF) can present with amyloid goiter. This is an autoimmune disorder that affects the Mediterranean littoral.⁴ These patients present with fevers and abdominal and chest pain. This condition can produce fibrillar depositions of amyloid protein, usually affecting the kidney⁵ but rarely involving the thyroid. We present a case of a 21-year-old woman with no medical history who presented to our hospital with a nontoxic diffuse goiter with initial presentation and pathologically confirmed as amyloid deposition secondary to FMF.

The patient is a 21-year-old Asian American woman with no significant medical history. She presented to our institution with dyspnea and dysphagia. An ultrasound from an outside hospital revealed diffuse thyroid enlargement. Our in-house laboratory results showed normal TSH, T4, T3, and elevated TPO antibody and erythrocyte sedimentation rate. A CT scan was performed on the patient showing heterogenous thyromegaly wrapping around the trachea and esophagus (Figure 1). A fine needle aspirate was performed, which showed a fibroinflammatory lesion. The patient started on steroids with no improvement, and a total thyroidectomy was performed. Macroscopic examination revealed a poorly defined, firm mass with pale tan areas of discoloration (Figure 2). Microscopic examination revealed an atrophic thyroid parenchyma with diffuse adipose cell metaplasia and diffuse interfollicular deposition of acellular amorphous material consistent with amyloid (Figure 3). Multifocal areas of chronic inflammation were also seen. Congo red stain was positive for amyloid (Figure 4A) with apple-green birefringence under polarized light (Figure 4B). Liquid chromatography tandem mass spectrometry was performed on peptides extracted from the Congo red-positive/microdissected areas of the paraffin-embedded thyroid specimen. The detected peptide profile was consistent with AA (SAA)-type amyloid deposition. The patient consequently had genetic testing showing a homozygous E148Q mutation. This confirms the clinical syndrome of FMF. After continuous follow-up, 10 years later, she developed end-stage renal failure with a renal biopsy confirming Renal AA amyloidosis. Since then, she has been on hemodialysis and is now on the waiting list for a

Around a billion individuals worldwide have hypertension. Of these, 95% have essential hypertension, a type of undiagnosed hypertension.¹ The regulation of blood pressure (BP) involves numerous signaling pathways. Among them, the Renin Angiotensin System is well known. All these pathways are regulated by modulation of renal salt handling and tone of vascular smooth muscle (VSM) tissue. Any of these mechanisms can become faulty and alter the resistance arteries’ VSM tone, which can elevate BP. However, since the exact origin of PH and its pathophysiology are unknown, less effective, and generic treatments are used.² The fact that more than 50% of hypertension patients in the USA do not have their BP under good control serves as an illustration of this. Antihypertensive treatment resistance affects an additional 5 million people and is defined as the inability to regulate BP despite the use of at least three antihypertensive drugs in combination.³

Increasing age, racial variables, history in household members, obese status, physical inactivity, larger amounts of salt consumption, stress, tobacco use, and heavy alcohol use are some of the potential etiological factors for essential hypertension.⁴ It has been examined in previous meta-analyses how vitamin D supplementation affects BP,⁵ but it is still unclear whether this connection is causal in the general population. This study focused on finding out the effect of vitamin D3 deficiency on BP.

Vitamin D, a steroid hormone, promotes the calcium and phosphate absorption from the gastro-intestinal tract (GIT) and reabsorption from the renal tubules. At low levels, it causes bone mineralization. At high doses, it causes bone resorption. It contributes significantly to mineral metabolism and skeletal homeostasis in this way.³

Up to 80% of human vitamin D comes from vitamin D3, which is produced in the skin by ultraviolet (UV) radiation from 7-dehydrocholesterol. Fish, egg yolk, fortified milk, cereal, juice, and yogurt are dietary sources of vitamin D that provide D2 as well as D3 forms and account for around 20% of the body's requirement. The significant vitamin D form, 25-hydroxyvitamin D [25(OH)D], is produced by the liver from D2 and D3 forms of vitamin D in the body. It is the most accurate measure of the action status and levels of vitamin D. It mostly depends on the serum vitamin D binding protein.⁴

According to the Institution of Endocrinology clinical practice guidelines, blood 25-hydroxyvitamin D [25(OH)D] results below 20 ng/mL (or 50 nmol/L) are considered deficient levels of vitamin D. Inadequate vitamin D status is ubiquitous among Chinese.⁴ Numerous studies have been published describing how vitamin D deficiency can lead to cancer,^6-10 metabolic disor

Lyme disease is the most common vector-borne illness in the United States and has been causing significant morbidity since its discovery in 1977. It is well-documented that about 10% of patients properly treated with antibiotics never fully recover, but instead go on to develop a chronic illness dubbed, posttreatment Lyme disease syndrome (PTLDS) characterized by severe fatigue, cognitive slowing, chronic pain, and sleep difficulties. This review includes 18 studies that detail the symptoms of patients with PTLDS and uses qualitative analysis to compare them to myalgic encephalitis/chronic fatigue syndrome (ME/CFS), a strikingly similar syndrome. In the majority of the PTLDS studies, at least four of the six major symptoms of ME/CFS were also noted, including substantial impairment in activity level and fatigue for more than 6 months, post-exertional malaise, and unrefreshing sleep. In one of the included PTLDS articles, 26 of the 29 ME/CFS symptoms were noted. This study adds to the expanding literature on the post-active phase of infection syndromes, which suggests that chronic illnesses such as PTLDS and ME/CFS have similar pathogenesis despite different infectious origins.

Capecitabine is an oral prodrug of 5-fluorouracil (5-FU), which is widely used for adjuvant and neoadjuvant chemotherapy of different solid tumors, particularly breast and colorectal cancers.¹ Neurotoxicity of capecitabine has been consistently reported as capecitabine-induced toxic leukoencephalopathy, which includes bilateral lesions in the corpus callosum and corticospinal tract presenting as acute or delayed central nervous system toxicity.² This side effect requires discontinuation of chemotherapy³; however, neurological symptoms due to capecitabine are reported to be usually reversible upon drug withdrawal.¹

The patients presenting with acute stroke-like symptoms with accompanied restricted diffusion outside typical vessel territory pose a significant diagnostic challenge. In the case of exclusively white matter involvement, the observed low apparent diffusion coefficient (ADC) could be due to the severe intramyelinic edema and not cell death, that is, cytotoxic edema. Multifocal leukoencephalopathy has been associated with capecitabine, but only a few cases have been reported in the literature.⁴

A 51-year-old woman was admitted due to acute onset of dizziness, dysarthria, and right-sided central facial paresis. The patient had been diagnosed with bilateral breast cancer 5 years ago for which neoadjuvant chemotherapy was done as well as surgical and radiation therapy. The primary tumor was a moderately differentiated invasive breast carcinoma of nonspecific type (right breast: stadium cT1b, human epidermal growth factor receptor 2 [HER2] negative with Ki67 10%–20%, and left breast: Stadium cT1c cN1 cM0. HER2 negative. Ki67 10%). Neoadjuvant chemotherapy regime consisted of four cycles of epirubicin/cyclophosphamide (every 2 weeks [q2w]) afterwards four cycles of paclitaxel (q2w) with granulocyte-colony-stimulating factor (G-CSF) support for 4 months. In the follow-up fluorodeoxyglucose-positron emission tomography (FDG-PET) scan, a solitary osseous metastasis was detected in the sacrum, for which capecitabine and bevacizumab had been initiated.

At our department, the patient reported a feeling of dizziness and difficulties in swallowing 1 day after starting capecitabine and bevacizumab. The CT at admission showed no infarction or hemorrhage and she was also outside thrombolysis therapeutic window. In the evening that day, there was a sudden onset of motoric aphasia. MR-tomography showed a pronounced hyperintense white matter lesion affecting the splenium of the corpus callosum and the medullary beds with pronounced fiber rarefication in arcuate fasciculus (Figure 1A–C). There was a mild pleocytosis of 15 cells/μL in the CSF, with normal protein and lactate. A JC virus polymerase chain reaction (PCR) from the CSF was negative. Onco-neural and antineuronal antibodies were all negative (Table 1). Clinical

Chronic obstructive pulmonary disease (COPD) can be prevented and treated through effective care, reducing exacerbations and hospitalizations. Early identification of individuals at high risk of COPD exacerbation is an opportunity for preventive measures. However, many patients struggle to follow their treatment plans because of a lack of knowledge about the disease, limited access to resources, and insufficient clinical support. The growth of digital health—which encompasses advancements in health information technology, artificial intelligence, telehealth, the Internet of Things, mobile health, wearable technology, and digital therapeutics—offers opportunities for improving the early diagnosis and management of COPD. This study reviewed the field of digital health in terms of COPD. The findings showed that despite significant advances in digital health, there are still obstacles impeding its effectiveness. Finally, we highlighted some of the major challenges and possibilities for developing and integrating digital health in COPD management.

The lung immune response consists of various cells involved in both innate and adaptive immune processes. Innate immunity participates in immune resistance in a nonspecific manner, whereas adaptive immunity effectively eliminates pathogens through specific recognition. It was previously believed that adaptive immune memory plays a leading role during secondary infections; however, innate immunity is also involved in immune memory. Trained immunity refers to the long-term functional reprogramming of innate immune cells caused by the first infection, which alters the immune response during the second challenge. Tissue resilience limits the tissue damage caused by infection by controlling excessive inflammation and promoting tissue repair. In this review, we summarize the impact of host immunity on the pathophysiological processes of pulmonary infections and discuss the latest progress in this regard. In addition to the factors influencing pathogenic microorganisms, we emphasize the importance of the host response.